Dupilumab

Indications

Dupilumab is used for: Atopic Dermatitis, Asthma, Chronic Rhinosinusitis

Adult Dose

Atopic Dermatitis Indicated for patients aged >12 years with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable 600 mg (ie, two 300-mg injections) SC once, and then 300 mg SC every other week Can be used with or without topical corticosteroids Topical calcineurin inhibitors may be used, but should be reserved for problem areas only (eg, face, neck, intertriginous, and genital areas) Asthma Indicated as an add-on maintenance treatment for moderate-to-severe asthma in patients aged ?12 years with eosinophilic phenotype or PO corticosteroid dependent asthma 400 mg SC once, then 200 mg q2weeks, OR 600 mg SC once, then 300 mg q2weeks For patients with PO corticosteroid-dependent asthma or comorbid moderate-to-severe atopic dermatitis (for which dupilumab is indicated), administer 600 mg initial dose then 300 mg q2weeks Chronic Rhinosinusitis Indicated as add-on maintenance treatment for adults with inadequately controlled severe chronic rhinosinusitis with nasal polyps (CRSwNP) 300 mg SC q2Weeks

Child Dose

Atopic Dermatitis Indicated for moderate-to-severe atopic dermatitis in adolescents aged ?12 yr whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable; may be used with or without topical corticosteroids <12 years: Safety and efficacy not established >12 years >60 kg: 600 mg (ie, two 300-mg injections) SC once, and then 300 mg SC every other week <60 kg: 400 mg (ie, two 200-mg injections) SC once, and then 200 mg SC every other week Topical calcineurin inhibitors may be used, but should be reserved for problem areas only (eg, face, neck, intertriginous, and genital areas) Asthma Indicated as an add-on maintenance treatment for moderate-to-severe asthma in patients aged ?12 years with eosinophilic phenotype or PO corticosteroid dependent asthma <12 years: Safety and efficacy not established >12 years 400 mg SC once, then 200 mg q2weeks, OR 600 mg SC once, then 300 mg q2weeks For patients with PO corticosteroid-dependent asthma or comorbid moderate-to-severe atopic dermatitis (for which dupilumab is indicated), administer 600 mg initial dose then 300 mg q2weeks

Renal Dose

Administration

SC Preparation Remove syringe from the refrigerator and allow to reach room temperature (45 min for 300-mg syringe or 30 min for 200-mg syringe) without removing the needle cap Inspect visually for particulate matter and discoloration prior to administration Dupilumab is a clear to slightly opalescent, colorless-to-pale yellow solution; do not use if the liquid contains visible particulate matter, is discolored, or is cloudy (other than clear to slightly opalescent, colorless-to-pale yellow) Does not contain preservatives; therefore, discard any unused product that remains in the syringe SC Administration For SC injection only May self-administer SC into the thigh or abdomen, except for the 2 inches around the navel May inject in the upper arm if administered by a caregiver For atopic dermatitis and asthma initial doses (ie, two 300-mg or two 200-mg injection), administer each injection at different injection sites Rotate injection site with each injection Do not inject into skin that is tender, damaged, bruised, or scarred

Contra Indications

Known hypersensitivity to dupilumab or its excipients

Precautions

Hypersensitivity reactions, including anaphylaxis, generalized urticaria, rash, erythema nodosum, and serum sickness or serum sicknesslike reactions, reported; if clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue dupilumab Conjunctivitis and keratitis reported more frequently in the treatment group during clinical trials for atopic dermatitis and CRSwNP; however, when treating asthma, incidence was similar to placebo Patients with asthma may present with serious systemic eosinophilia, including clinical features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis; these events may be associated with reduction of PO corticosteroids; monitor for rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy in patients with eosinophilia Do not use to treat acute bronchospasm or status asthmaticus Do not abruptly discontinue corticosteroid therapy upon initiation; reduce corticosteroid doses gradually, if appropriate, under physician supervision Instruct patients with atopic dermatitis or CRSwNP who have comorbid asthma not to adjust or stop their asthma therapy without consulting their physician Patients with pre-existing helminth infections were excluded from clinical trials; treat infections before initiating; if patient becomes infected and is unresponsive to antihelminths, discontinue dupilumab until infection resolves

Pregnancy-Lactation

Pregnancy Available data from case reports and case series on use in pregnant women have not identified drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; human IgG antibodies are known to cross the placental barrier; therefore, drug may be transmitted from mother to developing fetus; there are adverse effects on maternal and fetal outcomes associated with asthma in pregnancy In women with poorly or moderately controlled asthma, evidence demonstrates there is an increased risk of preeclampsia in mother and prematurity, low birth weight, and small for gestational age in the neonate; level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control Lactation There are no data on presence of dupilumab in human milk, effects on breastfed infant, or on milk production; maternal IgG is known to be present in human milk; effects of local gastrointestinal exposure and limited systemic exposure to dupilumab on breastfed infant are unknown; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Interactions

Avoid coadministration with live vaccines CYP450 substrates The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (eg, interleukin [IL]-1, IL-6, IL-10, TNF-alpha, IFN) during chronic inflammation Dupilumab may modulate serum levels of some cytokines Therefore, upon initiating or discontinuing dupilumab in patients who are receiving concomitant drugs that are CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for effect (eg, for warfarin) or drug concentration (eg, for cyclosporine) and consider dosage modification of the CYP450 substrate

Adverse Effects

Side effects of Dupilumab : 1-10% Injection site reactions (10%) Conjunctivitis (9-10%) Blepharitis (<1-5%) Oral herpes (3-4%) Keratitis (<1-4%) Immunogenicity, neutralizing (2%) Eye pruritus (1-2%) Other herpes simplex virus infection (1-2%) Dry eye (<1-2%) <1% Eosinophilia

Mechanism of Action

Monoclonal antibody that inhibits interleukin-4 (IL-4) and IL-13 signaling by specifically binding to the IL-4R-alpha subunit shared by the IL-4 and IL-13 receptor complexes Blocking the IL-4R-alpha subunit inhibits IL-4 and IL-13 cytokine-induced responses, including the release of proinflammatory cytokines, chemokines, and IgE